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      Correlations between ventricular enlargement and gray and white matter volumes of cortex, thalamus, striatum, and internal capsule in schizophrenia

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          Abstract

          Ventricular enlargement is one of the most consistent abnormal structural brain findings in schizophrenia and has been used to infer brain shrinkage. However, whether ventricular enlargement is related to local overlying cortex and/or adjacent subcortical structures or whether it is related to brain volume change globally has not been assessed. We systematically assessed interrelations of ventricular volumes with gray and white matter volumes of 40 Brodmann areas (BAs), the thalamus and its medial dorsal nucleus and pulvinar, the internal capsule, caudate and putamen. We acquired structural MRI ( patients with schizophrenia ( n = 64) and healthy controls ( n = 56)) and diffusion tensor fractional anisotropy (FA) (untreated schizophrenia n = 19, controls n = 32). Volumes were assessed by manual tracing of central structures and a semi-automated parcellation of BAs. Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain; a similar but less pronounced pattern was seen in normal controls; local correlations (e.g. temporal horn with temporal lobe volume) were not appreciably higher than non-local correlations (e.g. temporal horn with prefrontal volume). White matter regions adjacent to the ventricles similarly did not reveal strong regional relationships. FA and center of mass of the anterior limb of the internal capsule also appeared differentially influenced by ventricular volume but findings were similarly not regional. Taken together, these findings indicate that ventricular enlargement is globally interrelated with gray matter volume diminution but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule.

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          Sex differences in cortical thickness mapped in 176 healthy individuals between 7 and 87 years of age.

          Findings from previous magnetic resonance imaging studies of sex differences in gray matter have been inconsistent, with some showing proportionally increased gray matter in women and some showing no differences between the sexes. Regional sex differences in gray matter thickness have not yet been mapped over the entire cortical surface in a large sample of subjects spanning the age range from early childhood to old age. We applied algorithms for cortical pattern matching and techniques for measuring cortical thickness to the structural magnetic resonance images of 176 healthy individuals between the ages of 7 and 87 years. We also mapped localized differences in brain size. Maps of sex differences in cortical thickness revealed thicker cortices in women in right inferior parietal and posterior temporal regions even without correcting for total brain volume. In these regions, the cortical mantle is up to 0.45 mm thicker, on average, in women than in men. Analysis of a subset of 18 female and 18 male subjects matched for age and brain volume confirmed the significance of thicker gray matter in temporal and parietal cortices in females, independent of brain size differences. Further analyses were conducted in the adult subjects where gender differences were evaluated using height as a covariate, and similar sex differences were observed even when body size differences between the sexes were controlled. Together, these results suggest that greater cortical thickness in posterior temporal inferior parietal regions in females relative to males are independent of differences in brain or body size. Age-by-sex interactions were not significant in the temporoparietal region, suggesting that sex differences in these regions are present from at least late childhood and then are maintained throughout life. Male brains were larger than female brains in all locations, though male enlargement was most prominent in the frontal and occipital poles, bilaterally. Given the large sample and the large range of ages studied, these results help to address controversies in the study of central nervous system sexual dimorphisms.
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            Meta-analysis of regional brain volumes in schizophrenia.

            The authors' goal was to determine whether patients with schizophrenia differ from comparison subjects in regional brain volumes and whether these differences are similar in male and female subjects. They conducted a systematic search for structural magnetic resonance imaging (MRI) studies of patients with schizophrenia that reported volume measurements of selected cortical, subcortical, and ventricular regions in relation to comparison groups. They carried out a meta-analysis of the volumes of these regions in the patients with schizophrenia and the comparison subjects using a random effects model; they also used random effects regression analysis to examine the influence of gender on effect sizes. Fifty-eight studies were identified as suitable for analysis; these studies included 1,588 independent patients with schizophrenia. Assuming a volume of 100% in the comparison group, they found that the mean cerebral volume of the subjects with schizophrenia was smaller (98%), but the mean total ventricular volume of the subjects with schizophrenia was greater (126%). Relative to the cerebral volume differences, the regional volumes of the subjects with schizophrenia were 94% in the left and right amygdala, 94% in the left and 95% in the right hippocampus/amygdala, and 93% in the left and 95% in the right parahippocampus. Relative to the global ventricular system differences, the largest differences in ventricular subdivisions were in the right and left body of the lateral ventricle, where the volumes of schizophrenic subjects were 116% and 116%, respectively. For most regions, effect size was not significantly related to gender. Regional structural differences in patients with schizophrenia include bilaterally reduced volume of medial temporal lobe structures. There is a need for greater integration of results from structural MRI studies to avoid redundant research activity.
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              What happens after the first episode? A review of progressive brain changes in chronically ill patients with schizophrenia.

              Numerous imaging studies have revealed structural brain changes in schizophrenia. Decreases in brain tissue are accompanied by increases in ventricle volumes and cerebrospinal fluid. Whether or not these brain changes are progressive beyond the first episode is subject to debate. To assess if progressive brain changes occur in chronically ill patients, 11 longitudinal magnetic resonance imaging and computed tomography studies were reviewed. Patients were ill for on average 10 years at their initial scan. Follow-up intervals varied between 1 and 10 years. Overall, the findings suggest continuous progressive brain tissue decreases and lateral ventricle volume increases in chronically ill patients, up to at least 20 years after their first symptoms. The extent of progressive brain tissue decrease in patients (-0.5% per year) is twice that of healthy controls (-0.2% per year). These findings are consistent with the extent of postmortem brain tissue loss in schizophrenia. Progressive volume loss seems most pronounced in the frontal and temporal (gray matter) areas. Progressive lateral ventricle volume increases are also found. More pronounced progressive brain changes in patients is associated with poor outcome, more negative symptoms, and a decline in neuropsychological performance in one or some of the studies, but not consistently so. Higher daily cumulative dose of antipsychotic medication intake is either not associated with brain volume changes or with less prominent brain volume changes. The progressive brain changes present in chronic schizophrenia may represent a continuous pathophysiological process taking place in the brains of these patients that warrants further study.
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                Author and article information

                Contributors
                +1-949-3153079 , mbuchsbaum@ucsd.edu
                Journal
                Eur Arch Psychiatry Clin Neurosci
                European Archives of Psychiatry and Clinical Neuroscience
                Springer-Verlag (Berlin/Heidelberg )
                0940-1334
                1433-8491
                24 March 2011
                24 March 2011
                October 2011
                : 261
                : 7
                : 467-476
                Affiliations
                [1 ]Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1230, 10029 New York, NY USA
                [2 ]Schizophrenia Clinic Program, Department of Psychiatry, Hospital Clínic Barcelona, Villarroel 170, 08036 Barcelona, Spain
                [3 ]Laboratory of Functional Neuromorphology, Clinica Universitaria, Universidad de Navarra, Avda. Pío XII 36, 31008 Pamplona, Spain
                [4 ]Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, University of Verona, Policlinico Giambattista Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy
                [5 ]Department of Psychiatry, James J Peters VA Medical Center, 130 West Kingsbridge Road, 10468 Bronx, NY USA
                [6 ]Departments of Psychiatry and Radiology, NeuroPET Center, University of California, 11388 Sorrento Valley Road, Suite #100, 92121 San Diego, CA USA
                Article
                202
                10.1007/s00406-011-0202-x
                3182327
                21431919
                19007d91-5132-4e3c-ad8f-5522b2d061fa
                © The Author(s) 2011
                History
                : 14 June 2010
                : 15 February 2011
                Categories
                Original Paper
                Custom metadata
                © Springer-Verlag 2011

                Neurosciences
                cerebral spinal fluid,fronto-thalamic connectivity,myelin,sulcal enlargement
                Neurosciences
                cerebral spinal fluid, fronto-thalamic connectivity, myelin, sulcal enlargement

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